This competitive grant application seeks continued support of the International Research Scientist Development Award (IRSDA) from Fogarty International Center of NIH. As part of the first funding period (9/2002 to 8/2005), we have successfully established local contacts, built resources and infrastructure, and collected family material for linkage studies to identify type 2 diabetes mellitus (T2DM) genes in an endogamous population of Khatri Sikhs in North India. With limited resources, we have already collected 324 sib pair families with 515 affected sib pairs (ASPs). We have named this Phase-l of the Sikh Diabetes Study (SDS). The NHLBI's Mammalian Genotyping Services will perform a whole-genome scan on the Phase-l family sample. We expect that the genome-wide scan of Phase-l will be completed by the end of 2005. We propose following aims for this renewal application: Aim 1: To carry out linkage analyses to map the location of T2DM susceptibility loci. Aim 2: To recruit a large size case-control cohort 700 cases and 700 controls from the Khatri- Sikh community as a resource for future association studies. Aim 3: To screen selected biological candidate genes falling under linkage peaks (Aim 1) by case-control association studies. We recently submitted an exploratory R21 grant to NIDDK to perform linkage analysis on the genome scan data and to also initiate a pilot case-control study. Since the outcome of R21 is uncertain, we have tentatively proposed to perform linkage analysis as part of this renewal (Aim 1). However, if the R21 application is funded, we will instead focus on collecting an even larger case-control cohort of 1,500 cases and 1,500 controls (Aim 2) and on screening some candidate genes (Aim 3). We believe that our study is unique and novel and there is a high probability that it will yield new information on genetic basis of T2DM in Indians. Renewal of this award will help by strengthening the Indo-US collaboration established during Phase-l of SDS for addressing a major public health problem of a developing country. Continued support of IRSDA at the conceptual stage of study will substantially promote the scientific development of the candidate to enable her to ultimately achieve a productive International career. [unreadable] [unreadable]